Phenotypes Associated with This Genotype

Genotype
MGI:5526018

• Allelic Composition: Abcb4^tm1Bor/Abcb4^tm1Bor
• Genetic Background: C.129P2-Abcb4^tm1Bor

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

decreased circulating calcium level ( J:199949 )

increased circulating phosphate level ( J:199949 )

decreased vitamin D level ( J:199949 )

• 25(OH)-vitamin D serum concentrations are almost 50% lower than in wild-type mice

increased transforming growth factor beta level ( J:199949 )

• increase in serum levels of activated TGF-beta until the age of 30 weeks which subsequently declines to basal levels by 45 weeks of age compared to wild-type mice which show a continuous decrease throughout life

increased tumor necrosis factor (ligand) superfamily member 11 level ( J:199949 )

• increase in serum levels of the osteoclastogenesis inducing factor RANKL

abnormal enzyme/coenzyme activity ( J:199949 )

• elevation in serum activities of liver enzymes, including aminotransferase and alkaline phosphatase

increased alkaline phosphatase activity ( J:199949 )

liver/biliary system

liver fibrosis ( J:199949 )

• liver damage increases most rapidly in the first 15 weeks of life and then progresses slowly thereafter

skeleton

decreased bone mineral content ( J:199949 )

• reduction of whole body bone mineral content in males and of bone fractions of the total tissue weights in females at 15 weeks of age

• decrease in femoral mineral contents

decreased bone mineral density ( J:199949 )

♀ • females fed a vitamin D insufficient diet exhibit decreased cortical bone mineral density compared to wild-type mice on the same diet

♀ • vitamin D supplementation does not restore bone abnormalities

decreased bone mineral density of femur ( J:199949 )

♀ • females fed a vitamin D insufficient diet exhibit decreased femoral bone mineral density compared to wild-type mice on the same diet

♀ • vitamin D supplementation does not restore bone abnormalities

decreased bone volume ( J:199949 )

• decrease in femoral mineral contents and in total femoral volume at 15 weeks of age, thus total femoral volume bone mineral density is not affected

abnormal compact bone morphology ( J:199949 )

♀ • females exhibit a decrease in cortical bone density and a lower circumference of the bone at the exact mid-diaphysis (periosteal circumference), resulting in normal thickness of the cortical bone

abnormal trabecular bone morphology ( J:199949 )

• increase in trabecular separation at 20 weeks of age

• trabecular tissue mineral density is lower at 30 weeks of age

• with increasing age, changes in trabecular order and connectivity are seen with reduced mineralization of the trabecular bone meshwork

abnormal trabecular bone volume ( J:199949 )

• changes in trabecular bone volume fractions are seen at 5 weeks of age but not in older mice, however trabecular thickness does not differ from wild-type

decreased bone trabecula number ( J:199949 )

• decrease in trabecular numbers at 20 weeks of age

decreased trabecular bone connectivity density ( J:199949 )

• connective density is lower at 20 weeks of age

abnormal bone remodeling ( J:199949 )

• mutants exhibit altered gene expression of bone modeling markers and an increase in serum levels of the osteoclastogenesis inducing factor RANKL, indicating impaired bone remodeling

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
cholestasis		DOID:13580		J:199949